Method and Device to Treat and Prevent Dialysis Graft Failure

ABSTRACT

A treatment assembly is positioned along an AV-fistula and couples therapeutic energy to an adjacent area due to a material response to an applied energy field from a remotely located energy source. The treatment assembly may be delivered into the fistula through a hemodialysis needle, or may be secured to the fistula graft itself and implanted therewith in a patient. A cover provides a shield between an anastomosis area and blood flow. Another AV-fistula includes a valved reservoir that receives a fluid agent from a hemodialysis needle while moving the needle into or from the fistula; the agent leaks from the reservoir into the fistula lumen. Another valved fistula is adjustable between an open condition and closed conditions during and between hemodialysis treatments, respectively. Another AV-fistula has a bladder reservoir coupled to a second refillable fluid reservoir and is adapted to locally deliver a therapeutic agent into the fistula lumen.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of patent application Ser. No.11/425,106 filed Jun. 19, 2006, which is a divisional of U.S.application Ser. No. 10/177,721, which was filed on Jun. 20, 2002 andwhich claims priority from U.S. provisional application Ser. No.60/299,223 filed on Jun. 20, 2001, all of which are incorporated hereinby reference.

STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT

Not Applicable

REFERENCE TO A COMPUTER PROGRAM APPENDIX

Not Applicable

BACKGROUND OF THE INVENTION

1. Field of the Invention

This invention pertains generally to hemodialysis, and more particularlyto hemodialysis systems and methods including A-V fistula grafts, A-Vfistula graft treatment systems, systems for treating a conditionassociated with an AV-fistula graft, and an A-V fistula graft systems.

2. Description of the Background Art

Renal disease and deficiency has long been a significant problem thatcontinues to plague an enormous population of patients, and the relatedcost of treatment continues as an ever growing burden on modern societyas a whole. For example, in 1996, there were 250,000 patients in the USwith end stage renal disease (ESRD), a number expected to grow by 10-15%per year over the next 20 years primarily as a result of an agingpopulation and advances in treatments for other diseases. The cost ofESRD in the US was $20 billion in the year 2000, 5% of all Medicareresources.

Dialysis involves cannulation of the vascular system for extracorporealflow of blood through a dialysis machine, which acts as a filter. Tofilter the blood efficiently, the dialysis machine requires 300-400ml/min of flow for approximately three hours three times per week. Tosupply this high a flow rate, a large vein is required which willprovide a flow rate of at least 300-400 ml/min. Otherwise, the vesselwill collapse as the dialysis machine pulls out blood.

Various central venous devices and methods have been disclosed thatprovide this generally required level of flow. Examples of such devicesinclude, without limitation, “TESSIO™” and “QUINTON™” catheters, whichare commercially available from Medical Components and Kendall (owned byTyco International) corporations, respectively. In general, thesedevices are inserted into the subclavian or internal jugular veins,communicate exteriorly of the patient, and at best are considered“semi-permanent” devices in that their longevity is limited, generallylasting up to a typical maximum of about 4 months.

The primary “long-term” solution generally involves gaining peripheralvessel access, most typically in an accessible region of a patient'sarm. This generally requires a surgical procedure, wherein an artery issurgically attached to a vein, either directly or via an artificialconduit that creates an arterio-venous fistula, such as for example aconduit made from polytetrafluoroethylene (PTFE) or a woven polyestersuch as Dacron™. This procedure essentially short-circuits the normalblood path to the hand, and can provide a flow of approximately 1liter/min. The conduit fistula is typically coupled to the correspondingarteries, such as by suturing, at locations called arterial and venous(respectively) “anastomoses”. According to the typical dialysisprocedure, the dialysis fistula is connected to a dialysis machine viadialysis needles that puncture the fistula conduit at a location betweenthe anastomoses. Blood traveling from the fistula through the needlesare carried by tubing into a dialyzer, which cleanses the blood byremoving waste matter, and returns the blood via another needle to thefistula. A typical blood cleansing procedure lasts about 3 hours, afterwhich the dialysis needles are removed and pressure is held at the siteof needle entry. Most patients require dialysis about three times perweek. A damaging process called “intimal hyperplasia” often begins atthe time of surgery, and continues undisturbed in most cases until itleads ultimately to failure of the access fistula.

In common practice, an artificial conduit is used 70% of time, as hasbeen previously disclosed by Stehman-Breen et al., “Determinants of typeand timing of initial permanent hemodialysis vascular access,” KidneyInternational, 57 (2000) 639-645. However, about 50% of these graftshave been observed to malfunction within 2 years of implantation, as hasbeen previously published by Diskin, C J et al., “PharmacologicIntervention to Prevent hemodialysis Access Thrombosis,” Nephron1993:64(1-26). A study by Tellis, V. A. et al., “ExpandedPolytetrafluoroethylene Graft Fistula for Chronic Hemodialysis,” Ann.Surg., Vol 189(1), 1979, pp 101-105, revealed a 62% primary patency ratein PTFE grafts. It is not believed that this number has changedsignificantly since this study despite enormous advances in technologyin other fields. The disclosures of the reference articles provided inthis paragraph are incorporated herein in their entirety by referencethereto.

The creation of such a fistula increases flow to the arm and hence tothe dialysis machine. The major problem in permanent dialysis access isthe longevity of the fistula. With current methods, fistula survival isgenerally about 8-12 months with artificial conduits, and generallyabout 2-3 yrs with autogenous conduits. In fact, it is believed thatabout 3 “revision procedures” are required for every new fistulacreated. Each revision procedure requires a new access site on thepatient's body. While the new fistula matures, a semi-permanent catheterneeds to be placed in a large central vein. This usually leads tosubstantial morbidity, cost, and physician frustration; and in 1993vascular access was described as a $1 billion problem. In a studypublished by Arora, P. et al., “Hospital Utilization among ChronicDialysis Patients,” J. Am. Soc. Nephrol., 11: 740-746, 2000, 36% of allhospital admission for dialysis patients was for matters related toaccess. Patients on dialysis require an average of about 2.2hospitalizations and about 14.8 hospital days per year related todialysis access. Many patients die secondary to lack of access. In anearlier study cited by Swapna, J. et al. in “Vascular Access Problems inDialysis Patients,” Heart Disease 2001; 3:242-247, about 18% of deathsin the dialysis population was due to lack of access. Though this numbermay have decreased in recent years as devices and techniques improve, itstill remains a significant issue that deserves attention. Thedisclosures in the reference articles cited in this paragraph are hereinincorporated in their entirety by reference thereto.

Morbidity related to fistulas fall into several categories, the mostcommon of which (e.g. about 95%) is clotting of the graft. Infectionoccurs in 18% of complications and pseudoaneurysm in about 2%. Theclotting pathophysiology can be further subdivided into clottingsecondary to a venous stenosis (about 55% of cases), or secondary to anarterial stenosis (about 10% of cases). Other reasons for clottinginclude hypotension and pressure to curtail bleeding following adialysis session.

Access to a fistula currently entails placement of a needle through theskin and into the fistula with subsequent attachment to a dialysismachine. The placement of the needle is not standardized with respect tothe fistula, being placed in a different spot in the graft each time,resulting in disruption of the ultrastructure of the material over time.Twenty (20%) percent of fistula failures occur at the site of needleentry and manifest as thrombosis, pseudoaneurysms, and aneurysms.Furthermore, at least about 10 minutes of pressure is usually requiredto prevent hematoma formation at the access site, which may itself leadto a thrombosis.

Various devices and methods intended to treat AV-fistula stenoses withlocalized energy delivery have been disclosed. For example, severaldevices and methods have been disclosed for delivering ultrasound energyto an anastomosis region.

At least one example of this type is intended to deliver ultrasoundenergy to the area of an existing fistula thrombosis in combination withdelivery of an echo contrast agent into the area to enhance theultrasonic affects at the thrombosis. The ultrasound energy may bedelivered transcutaneously to the area, or intravascularly such as byuse of a miniature ultrasonic transducer located on a catheter insertedwithin the fistula. However, this particular technique suffers by therapid clearance that the contrast agent may experience from the area ina blood flow environment. Also, this example does not provide for adevice or method for using energy delivery for regular preventativemaintenance of fistula patency, such as to prevent thrombus formation oradhesion in the fistula, or to prevent or treat neo-intimal hyperplasia.

At least one other example also includes a system and method fordelivering ultrasound to the anastomotic junctions of fistulas in orderto inhibit substantial neo-intimal hyperplasia by use of an ultrasoundtransducer located on an internal catheter probe within the fistula, orwith a focused ultrasound transducer assembly associated with anexternal ultrasound energy source. However, this example does notprovide for prevention or removal of thrombus. In addition, the internalcatheter aspect of this example requires an active ultrasound energysource to be located on the catheter itself, which results insignificant complexity and cost that may be prohibitive to regularmaintenance use as a disposable assembly. The active source in additionmay limit the ability to make such a catheter sufficiently small to beinserted into a fistula lumen through certain needles such as certainhemodialysis needles.

In addition to the limitations of the previous ultrasound energydelivery examples just described, they also do not provide for a systemor method for actuating an treatment device within a fistula to delivervibratory or other energy to tissues by exposing the treatment assemblyto an applied energy field from a remotely located energy source outsideof the fistula, such as externally of the patient and transcutaneouslyacross a skin barrier. Nor do these previous techniques provide for theability to deliver an energy delivery treatment assembly into a fistulathrough a hemodialysis needle such that additional punctures of thefistula are not required. Still further, these previous techniques alsodo not provide for an energy delivery treatment assembly secured to andimplanted with a fistula graft. Nor do these techniques provide forother forms of energy delivery than ultrasound into problematic areasassociated with fistula grafts in order to provide therapy to a patient.

Another example of a previously disclosed device system and methodprovides for delivery of a doppler ultrasound monitoring transducer intoa fistula through a hemodialysis needle. However, the doppler device andmethod of this example does not deliver energy into the fistula in orderto affect treatment or prevention of stenosis associated with thefistula. Other beneficial forms of energy delivery other than dopplerultrasound also are not provided according to this example. Moreover,there is no provision for applying an energy field from outside of afistula to actuate energy delivery from a treatment assembly locatedwithin the fistula.

Various previous disclosures that provide additional backgroundinformation and further illustrate the context of various aspects ofmedical device systems and methods herein summarized or describedinclude the following issued U.S. patents: U.S. Pat. No. 3,225,129 toTaylor et al.; U.S. Pat. No. 3,953,566 to Gore; U.S. Pat. No. 3,962,153to Gore; U.S. Pat. No. 4,187,390 to Gore; U.S. Pat. No. 4,267,863 toBurelle; U.S. Pat. No. 4,536,018 to Patarcity; U.S. Pat. No. 4,787,921to Shibata et al.; U.S. Pat. No. 6,019,788 to Butters et al; U.S. Pat.No. 6,102,884 to Squitieri; and U.S. Pat. No. 6,153,252 to Hossainy etal. The disclosures of these references are herein incorporated in theirentirety by reference thereto.

Other previously disclosed devices and methods that disclose additionalbackground information related to at least one of fistulas, valves,renal interventions, or dialysis may be reviewed by reference to thefollowing issued U.S. patents: U.S. Pat. No. 4,822,341 to Colone; U.S.Pat. No. 5,454,374 to Omachi; U.S. Pat. No. 5,562,617 to Finch et al.;U.S. Pat. No. 5,690,115 to Feldman et al.; U.S. Pat. No. 5,702,715 toNikolaychik et al.; U.S. Pat. No. 5,879,320 to Cazenave; U.S. Pat. No.6,086,573 to Siegel et al.; U.S. Pat. No. 6,113,570 to Siegel et al.;U.S. Pat. No. 6,177,049 to Schnell et al; U.S. Pat. No. 6,319,465 toSchnell et al.; and U.S. Pat. No. 6,387,116 to McKenzie et al. Thedisclosures of these references are also herein incorporated in theirentirety by reference thereto.

Despite certain advances that may have been provided by various of thedisclosures cited above, there are still many needs that have not yetbeen adequately met.

There is still a need for a hemodialysis system and method that providesfor improved longevity and patency of AV-fistula implants.

There is in particular still a need for a hemodialysis system and methodthat substantially prevents or removes occlusive stenoses associatedwith AV-fistula implants.

There is also a need to accomplish the foregoing while minimizingmorbidity and without the use of substantially invasive interventions.

There is also in particular a need to provide for routine, therapeuticenergy delivery into localized areas associated with implanted fistulasusing disposable energy coupling assemblies that are cost effective andthat may be delivered using conventional hemodialysis needles.

BRIEF SUMMARY OF THE INVENTION

The present invention generally comprises hemodialysis systems andmethods, including, without limitation, A-V fistula grafts, A-V fistulagraft treatment systems, systems for treating a condition associatedwith an AV-fistula graft, and an A-V fistula graft systems.

One object of the invention is to provide a hemodialysis system thataccomplishes the foregoing needs that have not been heretofore met bypreviously disclosed systems.

Accordingly, one aspect of the hemodialysis system includes at least onetreatment assembly that is adapted to be positioned at a location alongan AV-fistula graft implant extending between an artery and a vein. Thetreatment assembly is adapted to couple energy between the treatmentassembly and an area adjacent to the treatment assembly sufficient toprovide a therapeutic effect within the AV-fistula.

In one mode of this aspect, the treatment assembly is adapted to belocated along an end portion of the AV-fistula graft that is adapted tobe anastomosed between the artery or vein. According to one embodimentof this mode, the treatment assembly is adapted to be located along theposition at a graft end portion that is anastomosed to the vein. In onefurther variation of this embodiment, the treatment assembly is adaptedto be located at either of two positions along each of two respectivegraft end portions, respectively, that are adapted to be anastomosed tothe vein and artery, also respectively.

In another mode, two treatment assemblies are provided and are adaptedto be located along each of two end portions of the AV-fistula graft,respectively, that are adapted to be anastomosed to the vein and artery,also respectively.

In another mode, the treatment assembly is located along a distal endportion of an elongate body of a catheter device.

In one beneficial embodiment of this mode, the distal end portion andtreatment assembly are adapted to be delivered to the location through ahemodialysis needle and into the graft extending between the vein andartery anastomoses.

In a further embodiment, the distal end portion is adapted to track overa guide wire to the location within the AV-fistula graft in-situ. Inanother embodiment, the distal end portion has a deflectable shape bymanipulating a deflection member extending from a proximal end portionof the catheter body and the distal end portion.

In still a further embodiment of this mode, the treatment assembly hasan expandable member that is expandable between a radially collapsedcondition and a radially expandable condition. In the radially collapsedcondition, the expandable member has a first outer diameter that isadapted to be delivered to the location within a lumen of the graftthrough the hemodialysis needle. In the radially expanded condition, theexpandable member has a second larger outer diameter and the treatmentassembly is adapted to couple energy to the area adjacent the expandablemember in the expanded condition.

In one further variation of this embodiment, the treatment assembly isadapted to couple energy to a circumferential area surrounding theexpandable member in the radially expanded condition. In another furthervariation, the expandable member is an inflatable balloon. One featureof the inflatable balloon includes a highly elastomeric material, whichmay be chosen in beneficial examples from polyurethane, silicone, orlatex rubber, or combinations or blends thereof. In an alternativefeature, the inflatable balloon is constructed of a relativelynon-compliant material such that the balloon is folded in the radiallycollapsed condition.

In another mode, the treatment assembly is adapted to be implanted atthe position along an AV-fistula graft.

According to one embodiment of this mode, the AV-fistula graft includesa graft body and the treatment assembly is adapted to be secured to thegraft body at the location.

In one variation of this embodiment, the treatment assembly includes atleast one member that extends beyond one of two opposite ends of thetubular graft body. According to one feature of this variation, themember is a tubular member secured to the graft body and extendingbeyond the end. According to another feature, the treatment assemblycomprises a plurality of adjacent elongate members positioned around acircumference and extending longitudinally beyond the graft end. Themembers according to this feature are adapted to be positioned to coverthe anastomosis between the graft body end and the respective artery orvein with respect to blood flow, and may be substantially pliable anddeflectable under pressure of blood flow in order to cover theanastomosis region. A still further variation of this feature providesthe members along only a portion of a circumference surrounding alongitudinal axis of the graft body, which portion may be located alonga downstream side of an anastomosis between the graft and a vein orartery.

In another mode, the treatment assembly is adapted to be activated tocouple the energy to the area by first coupling energy between thetreatment assembly and a remotely located energy source. In oneembodiment, the treatment assembly is adapted to heat upon the energycoupling with the energy source. In another further embodiment, thetreatment assembly comprises a material that is adapted to receiveenergy from the energy source, which received energy activates thetreatment assembly to couple energy between the treatment assembly andthe area at the location. In one variation of this embodiment, thematerial is adapted to be ultrasonically actuated by a remote ultrasoundenergy source. In another variation, the material is a ferromagneticmaterial adapted to be inductively actuated under a magnetic field fromthe energy source. In another variation, the material is adapted toabsorb light from a light energy source, such as in one furthervariation UV light. In still a further variation, the material isadapted to receive electrical current energy from the remotely locatedsource.

In still another beneficial embodiment, the treatment assembly isadapted to couple energy from a remote energy source located across askin layer of the patient when the treatment assembly is located at theposition along the AV-graft fistula extending between vein and arteryanastomoses within the patient's body. In yet another mode, the systemmay further include the energy source in a combination kit with thetreatment assembly.

In another mode, the device is adapted to couple a sufficient amount ofenergy between the treatment assembly and the area to substantiallyinhibit formation of a stenosis associated with the AV-fistula implant.

In a further mode, the device is adapted to couple a sufficient amountof energy between the treatment assembly and the area to substantiallyremove at least a portion of a stenosis associated with the AV-fistulaimplant.

In another mode, the treatment assembly is adapted to couple sufficientenergy to the area to substantially prevent neo-intimal hyperplasia inthe area.

In another mode, the treatment assembly is adapted to couple sufficientenergy to the area to substantially prevent thrombogenesis or thrombusadhesion in the area.

In another mode, the distal end portion and treatment assembly isadapted to be delivered into the AV-fistula implant through a dialysisneedle.

In another mode, the device is adapted to couple the energy between thetreatment assembly and a substantially circumferential region of theAV-fistula circumscribing an internal lumen of the AV-fistula.

In another mode, the treatment assembly includes an adjustable memberthat is adjustable between a first shape having a first outer diameterthat is adapted to be delivered into the AV-fistula, and a second shapehaving a second outer diameter that is greater than the first outerdiameter.

According to one embodiment of this mode, the second outer diameter issufficient to couple the energy between the adjustable member and asubstantially circumferential region of the AV-fistula wall.

According to another embodiment of this mode, the adjustable member is aradially expandable member that is adjustable between a radiallycollapsed condition that characterizes the first shape and a radiallyexpanded condition that characterizes the second shape.

In one further variation of this embodiment, the radially expandablemember includes a radially expandable tubular member, which maybeneficially have the feature of being an inflatable balloon. Accordingto one highly beneficial version of this variation, the inflatableballoon is constructed from a highly compliant material, which furtherprovides further benefits if provided with a material exhibiting atleast 500% elongation between the radially collapsed and expandedconditions. Further exemplary embodiments providing such benefit mayinclude a balloon made from at least one of the following materials:polyurethane; latex; silicone; or derivatives, combinations, or blendsthereof. In a further version of the balloon variation, a valve assemblyis provided that is adapted to allow the balloon to be inflated withfluid pressure provided by a hemodialysis needle. Such valve assemblymay be beneficially positioned to allow such inflation duringadvancement of or withdrawal of the needle through the AV-fistula graftwall ancillary to a hemodialysis procedure.

In another mode, the treatment device is adapted to couple to anexternal energy source that is adapted to activate the treatmentassembly in order to couple the energy between the treatment assemblyand the area adjacent to the treatment assembly.

Another aspect of the invention provides a hemodialysis method thatincludes positioning a treatment assembly along a location of anAV-fistula graft extending between a vein anastomosis and an arteryanastomosis, and coupling energy between the treatment assembly and anarea adjacent to the treatment assembly such that a therapeutic orprophylactic affect is achieved within the AV-fistula graft.

In one mode of this aspect, the method includes first coupling energyfrom a remotely located energy source to the treatment assembly at thelocation, and then coupling energy between the treatment assembly andthe area.

One embodiment of this mode includes coupling the energy between theenergy source and the treatment assembly through tissue and withoutphysically connecting the energy source and the treatment assembly.

Another embodiment of this mode includes coupling the energy between theenergy source and the treatment assembly across a skin layer of thepatient. In another embodiment considered highly beneficial, the methodincludes heating the treatment assembly with the energy coupled from theenergy source, and thermally coupling the treatment assembly with thearea. In certain further beneficial variations of these embodiments, themethod may further include coupling ultrasound, light, inductive, orelectrical energy between the energy source and the treatment assembly.

Another mode of this aspect includes implanting the treatment assemblyat the location. One beneficial embodiment of this mode includesextending the treatment assembly beyond an end of the AV-fistula graft,and substantially covering an anastomosis region between the graft endand a respectively anastomosed region of vein or artery wall withrespect to blood flow.

Another mode of this aspect includes delivering the treatment assemblyto the location through a hemodialysis needle. One embodiment of thismode includes expanding an expandable member of the treatment assemblyat the location and coupling energy between the expandable member andthe area adjacent thereto.

Another mode of this aspect includes coupling sufficient energy betweenthe treatment assembly and the area to substantially prevent formationof a stenosis at the location.

Another mode of this aspect includes coupling sufficient energy betweenthe treatment assembly and the area to substantially reduce a stenosisat the location.

Another mode of this aspect includes coupling sufficient energy betweenthe treatment assembly and the area to substantially prevent localizedthrombus formation or adhesion at the location.

Another mode of this aspect includes coupling sufficient energy betweenthe treatment assembly and the area to substantially reduce a localizedthrombus at the location.

Another aspect of the invention is a hemodialysis system with anAV-fistula graft that includes a valve system coupled to a lumen of theAV-fistula graft and is adjustable between an open condition and aclosed condition with respect to the lumen. In the open condition, theAV-fistula graft is substantially adapted to allow substantial fluidcommunication between an arterial and a venous anastomosis. In theclosed condition, the fluid communication between the anastomoses issubstantially occluded.

According to one mode of this aspect, the valve system includes at leastone valve with an expandable member coupled to the AV-fistula lumen andthat is adjustable between a radially collapsed condition and a radiallyexpanded condition. The radially collapsed condition characterizes atleast in part the open condition for the valve system and allows forfluid communication between the anastomoses. The radially expandedcondition characterizes at least in part the closed condition for thevalve system and substantially occludes the fistula lumen. In oneembodiment of this mode, the expandable member is an inflatable balloon.In one variation of this embodiment, the valve system includes aninflation chamber that is adapted to allow the inflatable balloon to beinflated with pressurized fluid from a hemodialysis needle positionedwithin the inflation chamber. In another further variation, theinflation chamber is positioned to allow the hemodialysis needle toinflate the balloon without requiring an additional graft puncture withthe hemodialysis needle before or after performing hemodialysis with theneedle through the graft.

In another mode, the valve is located along an end portion of theAV-graft fistula that is adapted to be anastomosed to a blood vessel.

In yet another mode, the valve is located along an intermediate regionof the fistula graft between the two end portions adapted to beanastomosed between an artery and a vein, respectively.

In still another mode, the system includes two valves positioned alongtwo opposite ends, respectively, of the AV-fistula graft that areadapted to be anastomosed to an artery and vein, also respectively. Inone embodiment, the two valves are adapted to independently adjustedbetween the respective open and closed conditions. In anotheralternative variation, they are adapted to be adjusted together with acommon actuator.

Another aspect of the invention is a method for adjusting an AV-fistulagraft between an open condition and a closed condition. In the opencondition, the AV-fistula graft allows substantial fluid communicationbetween the arterial and venous anastomoses. In the closed condition,the AV-fistula graft substantially prevents fluid communication betweenthe arterial and venous anastomoses.

Another aspect of the invention is an AV-fistula graft that is adaptedto locally deliver a therapeutic fluid agent into a tissue area adjacentto the graft when it is implanted between arterial and venousanastomoses.

According to one mode of this aspect, the graft includes a reservoirthat is adapted to house the fluid agent and to elude the agent into thearea.

In one embodiment, the reservoir is a bladder assembly associated with agraft body extending between the anastomoses. In one variation, thebladder assembly is an annular shape circumscribing the graft lumen andis adapted to deliver the agent into the graft lumen. In a furthervariation, the annular bladder includes pores located to deliver theagent into the lumen.

In another embodiment, the reservoir is adapted to be fluidly coupled toa remotely located fluid source and to receive fluid agent from thesource for delivery into the lumen. In one variation, the systemincludes the remotely located fluid source. In a further variation, thefluid source is adapted to be implanted within the body of the patient.In another further variation, the fluid source is adapted to berefilled, such as with a syringe through a valve member associated withthe fluid source. In another further variation, the fluid source isadapted to be located externally of the patient's body.

Each of the various aspects provided above are considered to beindependently beneficial aspects of the invention, and is not requiredto be combined with the various other aspects or additional modes,embodiments, variations, or features provided. Notwithstanding theforegoing, the various combinations and sub-combinations of such aspectsand additional modes, embodiments, variations, and features also providefurther benefits and are thus considered to provide additional,independent value as would be apparent to one of ordinary skill basedupon review of the totality of this disclosure as provided below and inthe claims.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1A shows a schematic view of certain corresponding regions of anartery and a vein of a patient prior to anastomosing an AV-fistula tothose respective regions according to an initial stage of performing ahemodialysis procedure.

FIG. 1B shows a schematic view of the same regions of artery and vein asshown in FIG. 1A, except shows the artery and vein during one step of ahemodialysis procedure using a hemodialysis system according to theinvention that includes an AV-fistula with a valve assembly incombination with hemodialysis needles extending through the valveassembly and into the fistula.

FIG. 1C shows a schematic view of the same anatomy and hemodialysissystem as shown in FIG. 1A, except shows the hemodialysis system duringanother mode of use for providing a therapeutic agent to the AV-fistulacontemporaneous with or in between hemodialysis procedures.

FIG. 1D shows a schematic view of the same anatomy as shown in FIG.1A-C, and including the same AV-fistula with valve assembly shown inFIGS. 1B-C, except showing the valve assembly after removal of thehemodialysis needles from the fluid agent reservoir that allows forcontrolled delivery of the fluid agent contents into the lumen of theAV-fistula.

FIG. 2A shows an angular perspective view of one particular valveassembly that is adapted for use with an AV-fistula in a hemodialysissystem such as that shown in FIGS. 1B-D.

FIG. 2B shows an exploded top view of region 2B shown in FIG. 2A.

FIG. 2C shows an exploded top view of region 2C shown in FIG. 2B.

FIG. 2D shows a schematic side view of a hemodialysis needle positionedacross a skin layer and through a valved assembly similar to thatvariously shown in FIGS. 2A-C.

FIG. 3A shows a schematic view of similar anatomy to that shown in FIGS.1A-D, except shows the anatomy undergoing treatment with anotherhemodialysis system according to the invention with two valves coupledto the AV-fistula at respective locations adjacent to the fistula'sanastomoses with the vein and artery, respectively, wherein the systemis shown in one mode with both the valves in an open condition.

FIG. 3B shows a similar schematic view of the same anatomy and system asthat shown in FIG. 3A, except shows the system in another mode with bothvalves in the respective closed conditions.

FIG. 3C shows a similar schematic view of the same anatomy and system asthat shown in FIGS. 3A-B, except shows the system in another mode ofuse.

FIG. 4A shows a similar schematic view of the same anatomy to that shownin FIGS. 1A-D and FIGS. 3A-C, except shows another hemodialysis systemaccording to the invention with a single valve coupled to an AV-fistulalumen at a location between the vessel anastomoses at the AV-fistula'sends.

FIG. 4B shows a similar schematic view of the same anatomy andhemodialysis system as that shown in FIG. 4A, except shows the system inanother mode of use with the centrally located valve adjusted to an offposition that corresponds to a substantial blockage of blood flowbetween the artery and vein along the fistula.

FIG. 4C shows a similar schematic view of the same anatomy as that shownin FIG. 4B, except shows a modified system and mode of use wherein thevalve assembly associated with the AV-fistula is located along a regionof the fistula that more closely corresponds to one of the artery orvein than the other.

FIG. 4D shows a similar schematic view of the same anatomy and system asthat shown in FIG. 4C, except shows the system in another mode of usewith the valve assembly closed, the hemodialysis needles removed, and astatic field of fluid located within the fistula.

FIG. 5A shows an angular perspective view of one embodiment for a valveassembly that is adapted for use in a hemodialysis system such as thesystem shown in FIGS. 3A-C, and shows the valve assembly with bothvalves in an open condition similar to that shown in FIG. 3A withrespect to a reference AV-fistula shown in phantom.

FIG. 5B shows an exploded side view of one valve of the valve assemblyshown in FIG. 5A in the open condition with respect to one anastomoticregion of the AV-fistula shown in phantom.

FIG. 5C shows an exploded side view of the valve shown in FIG. 5B, butshows the valve in the closed condition with respect to the anastomoticregion of the AV-fistula shown in phantom.

FIG. 6A shows a longitudinally cross-sectioned view of a furtherAV-fistula embodiment according to the invention.

FIG. 6B shows an angular perspective view of one end of anotherAV-fistula embodiment according to the invention.

FIG. 6C shows a transverse cross-sectioned view taken along line 6C-6Cin FIG. 6B.

FIG. 6D shows an angular perspective view of an AV-fistula of theinvention similar to that shown in FIGS. 6B-C in one mode of use duringan end-to-end anastomosis procedure with a vein.

FIG. 6E shows a side perspective view of the AV-fistula and vein shownin FIG. 6D after a completed end-to-end venous anastomosis.

FIG. 6F shows partially cross-sectioned side view of a further variationof an AV-fistula such as that shown in FIGS. 6B-F, and shows the fistulaafter a completed “side” anastomosis with a vein shown schematically.

FIG. 6G shows a partially cross-sectioned top view of the AV-fistula andanastomosed vein shown in FIG. 6F.

FIG. 7A shows a longitudinally cross-sectioned view of anotherAV-fistula embodiment of the invention.

FIG. 7B shows a schematic view of another hemodialysis system accordingto the invention with an AV-fistula that is fluidly coupled to aremotely located fluid agent reservoir and locally administering fluidagent from the reservoir into the AV-fistula lumen.

FIG. 7C shows a partially segmented side view of one beneficialvariation for the AV-fistula shown in FIG. 7B that includes an annular,porous bladder located within a graft wall of the AV-fistula.

FIG. 7D shows an exploded angular perspective view of a further porousbladder variation adapted for use in an AV-fistula embodiment similar tothat shown in FIG. 7C.

FIG. 8A shows a further embodiment with an AV-fistula and a remotelylocated energy source, shown in shadow, and energy is shownschematically coupled between an end of the AV-fistula and the remotelylocated energy source across a tissue barrier such as the patient'sskin.

FIG. 8B shows a transverse cross-sectioned view through an anastomosisregion of a further AV-fistula embodiment that combines various aspectsof the embodiments shown in FIGS. 8A and 6B-D, respectively.

FIG. 8C shows a schematic side view of a further AV-fistula embodimentthat includes various aspects of the embodiments shown in FIGS. 8A-Bafter a completed side anastomosis to a vein shown in phantom and duringone mode of use in conjunction with a remotely located energy source.

FIG. 8D shows a partial, side perspective view of another AV-fistulaembodiment that also includes various aspects of the embodiments shownin FIGS. 8A-B after a completed end-to-end anastomosis to a vein andalso during one mode of use in conjunction with a remotely locatedenergy source.

FIG. 9A shows a schematic view of a catheter device embodiment of theinvention.

FIG. 9B shows a schematic view of another hemodialysis system of theinvention that includes the catheter device shown in FIG. 9A, and showsthe system during one mode of use in treating an AV-fistula connectingan artery and a vein.

FIG. 9C shows an exploded view of an area of the AV-fistula shown inFIG. 9B being treated by a distal treatment assembly of the catheterdevice.

FIG. 9D shows a schematic view of a transverse cross-section through atreatment device, such as provided by the catheter shown in FIGS. 9A-C,taken through an expandable member in a radially expanded condition, andshows in shadow the expandable member in a radially collapsed condition,and also schematically illustrates various aspects of energy couplingbetween the expandable member and an external energy source as well aswith surrounding tissues.

DETAILED DESCRIPTION OF THE INVENTION

It is to be appreciated that the present invention in one regardprovides a system with at least one device that is adapted to increasethe long-term patency for an AV-fistula, and therefore longevity ofdialysis access, with respect to a vein 2 and artery 4 in a patient,which are shown in FIG. 1A for the purpose of reference prior tobeginning a hemodialysis procedure with the system and method of thepresent invention.

AV-Fistula with Valved Needle Access & Controlled Drug Delivery

According therefore to one beneficial embodiment, FIG. 1 shows onehemodialysis system 1 of the invention with an AV-fistula 10 thatextends between two anastomosis sites 12,14 along vein 12 and artery 14,respectively. Along a wall of fistula 10, and generally flush with anouter surface thereof, is a localized valve system 50.

Valve system 50 may be integrated into fistula 10, such as in apre-packaged, sterilized assembly. However, it is further contemplatedthat valve system 50 may also be provided separately. In this variation(not shown), the valve may be manually inserted through an apertureformed in the graft wall of the fistula, which aperture may be itselfprovided by the graft supplier or may be formed by the end user such asduring initiation of the surgical procedure to create the AV-fistula.Per the latter example, this allows the positioning of the valveassembly to be customized by the user to meet the anatomic needs of aparticular patient, or according to the preference of the particularhealthcare provider performing the fistula implantation (or otherwisethe hemodialysis procedure). Moreover, it is also to be appreciated thatthe present system 1 is principally adapted for use with an artificialconduit; however, in certain limited instances it may be further adaptedfor use in an autogenous fistula.

In any event, valve system 50 has two components: 1 a first valveassembly that is generally a membrane 53, which sits above a secondvalve assembly 57 and demarcates a small reservoir 55. The cavity ofreservoir 55 according to one particular embodiment contains a bioactivefluid agent, such as for example an antithrombotic, anti-mitotic,anti-proliferative agent, or combination of one agent with anotherpharmaceutical or agent, both of which will preferably leach fromreservoir 55 and into lumen out in-between dialysis sessions.

As shown in FIGS. 1C-D, the reservoir 55 may be filled with fluid agentby use of the dialysis needles 70,80, such as during partial proximalwithdrawal after hemodialysis so that the fluid ports in the needle tips72,82, respectively, are located within reservoir 55. This allows fordelivery of the fluid agent without any additional intervention orvenous (or arterial) puncture beyond what is already being done for thehemodialysis. In addition, needles 70,80 may inject the agent fromsyringes or other pressurizeable source, such as is shown at sources75,85, respectively, which may be coupled to the syringes via a side armwhile the syringes are also coupled to the hemodialysis machine, orseparately coupled. Or, the hemodialysis machine may itself be adaptedto provide the fluid agent delivery to the needles.

Moreover, it is further contemplated that the fluid agent solution mayalso be refilled in between dialysis sessions. In any case, manydifferent elution profiles may be acceptable into lumen 13, dependingupon the particular need for a fluid agent, lumen diameter, fistuladwell-time, inter-treatment periods, etc. In many cases, however, theelution profile would be a slow leak rate of the pharmaceutical throughthe valve, over the 2-3 days between dialysis. As such, the mechanism bywhich such “controlled” elution is achieved should be tailored toaccomplish this objective according to the particular agent to bedelivered. For example, a porous membrane may be provided integral withvalve assembly 57, or along another wall bordering reservoir 55. Or,valve assembly 57 may not completely seal shut after it is opened topass needles 70,80 during dialysis. A controlled “leaky” valve may besufficient to achieve the desired results. However, as valve assembly 57is localized along fistula 10 in order to provide for standardizedneedle puncture site, drug delivery from reservoir 55 may not beaccomplished along other portions of fistula 10 if done only throughvalve system 50. For this reason, reservoir 55 according to furtherembodiment may be adapted to couple its contents to regions of fistula10 other than only where valve system 50 is located.

In use according to the present embodiment, fistula 10 and valve system50 are surgically implanted beneath a patient's skin. Trained personnelwould locate the valve system 50 in the fistula 10 via light touch andinsert a dialysis needle through the skin and then through the topmembrane in the valve assembly. Next, the needle would be furtherinserted through the valve and into the blood flow of the fistula. Thesame would be done for the second cannula. The result is shown in FIG.1B.

At the end of the dialysis session, the needles are removed. As eachindividual needle is removed, a pharmaceutical solution is injected intothe space between the membrane and the valve. This is shown in FIG. 1C,with one schematic view of the result shown in FIG. 1D for the purposeof further illustration.

According to this embodiment, bioactive fluid agent may be deliveredinto a localized reservoir associated with the fistula implant and byway of the hemodialysis needles, and such agent may then be deliveredinto the fistula lumen over a delayed period of time. Such system andmethod is highly beneficial for use with certain agents that are adaptedto prevent clotting, infection, and neointimal hyperplasia, or to removeor dissolve the same. Further examples of such fluid agents that areapplicable to the present embodiment, and to other embodiments hereinshown or described where appropriate, include, without limitation:Cisplatin™; rapamune (or Rapamycin™); pacliitaxel (or Taxol™); heparin;hirudin; hirulog; exochelin; aspirin; streptokinase; urokinase; TPA; orderivatives, combinations, or blends thereof.

It is also to be appreciated that, though various of the embodiments forlocal agent delivery are beneficially adapted for coupling and deliveryof fluid agents, such embodiments may also be adapted to store and/ordeliver agents in other forms than fluid, such as for example powder orgel suspension forms. For example, delivery of a powder agent within areservoir couple to a flow lumen of a fistula may be accomplishedaccording to certain of the present embodiments without departing fromthe scope of the invention.

FIGS. 2A-D show further details of one particular embodiment for valveassembly 57 by reference to valve system 50 and adapted for use in anAV-fistula such as according to system 1 as follows.

Valve assembly 57 includes a wall 60 with a matrix or plurality ofvalves 62 that form a patterned grid, as shown in FIG. 2A and inincreasing more detail in FIGS. 2B-D, respectively. More specifically,each valve 62 includes a plurality of moveable members 64 that aregenerally splines or struts and are adjustable between a first conditionor position and a second condition or position. The first condition ischaracterized by the members 64 being in a first position andcharacterizes the closed condition for the valve 62 and is generally aresting condition, shown in FIGS. 2B-C. The second condition ischaracterized by the members 64 in second relative positions andcharacterizes the open condition for the valve 62 and characterizes theopen condition, allowing a needle to pass therethrough (shown in FIG.2D). In the particular embodiment shown and by reference to FIG. 2D, themembers 64 are adjusted from the closed condition to the open conditionunder force from advancing needle 70 against splines 64. Members 64 aresufficiently resilient such that subsequent withdrawal of needle 70results in members 64 returning substantially back to their relativefirst positions, and thus substantially returning the valve 62 to theclosed condition.

While various specific variations for valves 62 may be acceptable,further more detailed features which are believed to be acceptable areas follows. Members 64 are constructed of a superelastic metal alloy,such as a nickel-titanium alloy, and more particularly Nitinol™. Members64 are formed from an initial foil or starting “blank” of the alloymaterial which is then processed to form members 64 in the integratedmesh shown, such as for example by photo etching, laser etching, orother suitable techniques. A typical starting foil may be between about0.25 and about 0.5 millimeters thick, with resulting matrix having thefollowing dimensions: width D of each valve being between about 1.25 andabout 1.5 times the size of the dialysis needle to be used therethrough,which needles often will be between about 1 and about 1.5 millimeters indiameter; the spacing between members 64 are generally between about 50and about 500 microns.

Members 64 may also be coated with a coating. In one regard, a coatingmay be adapted to aid in preventing influx of blood factors intoreservoir 55. Use of a hydrophobic coating, such as for example PTFE,may provide this result by surface tension effects through the gaps.Alternatively, a hydrophilic coating such as hydrogel may actuallyabsorb water components from the blood pool or from the fluid inreservoir 55. Upon such absorption the coating swells and functionally“closes the gaps” without significantly degrading the availableflexibility and therefore deflectability of members 64 as they areadjusted to their respective open positions under the force of theadvancing needle.

It is to be appreciated that small gaps may remain between members 64,which may be designed for optimized drug elution from reservoir 55 intothe graft lumen but resistance to blood factor influx. Therefore, thedimensions provided above may be adjusted according to the overallaffect desired, and including with respect to the coating chosen for aparticular assembly.

FIGS. 2A-D represent one beneficial embodiment for the valve assemblyshown schematically in FIGS. 1A-D. However, despite the particularbenefits of this embodiment, other alternative embodiments andvariations are contemplated, and the intended scope of the inventionshould in one regard be considered broadly. For example, in one regardthe valves 62 are generally considered to include a moveable member thatis adapted to be moved from a first position to a second position byadvancing a hemodialysis needle therethrough. In the first position, thevalves 62 are closed and reservoir 55 is substantially sealed from bloodleaking from lumen 13 of fistula 10. However, as mentioned above, suchfirst position may be incomplete just enough to allow for drug elutionfrom reservoir 55 and into lumen 13. In the second position shown,needle 70 passes into lumen 13 for hemodialysis treatment to beperformed. These beneficial aspects need not be limited to the specificgrating/cooperating spline embodiments shown, though they are inparticular considered beneficial. In fact, single panes of alloy mayreplace the plurality of splines for each of the plurality of valves 62,and swing like a door between the open and closed conditions. Or, ratherthan square shaped arrangements for valves 62, circular shapes may beused, such as by providing a plurality of pie-shaped windows thatcooperatively adjust between open and closed positions to open and closethe valve. Substantially elastic memory polymers may be used instead ofsuperelastic metal alloy, or other metals such as stainless steel may beused so long as the deflection does not result in such plasticdeformation that a seal can not be adequately achieved after repeat use.Or, other mechanisms such as deflectable seated ball bearing valves,hydraulic bladders, compressible annular members, or self-sealingmembrane materials (such as used for valve assembly 53, etc. may be usedin certain circumstances.

AV-Fistula with Adjustable Valve System

The embodiments shown in FIGS. 3A-4D generally relate to an AV-fistulawith a valved inner lumen, such that the fistula may be provided in anopen condition during dialysis, but in a closed condition betweendialysis procedures.

In the specific embodiment shown in FIGS. 3A-C, two valves 150,160 arelocated along the two opposite end portions 112,114, respectively, offistula 110 that are anastomosed to vein 2 and artery 4, alsorespectively. According to use of these valves 150,160, the entirefistula 110 can be turned “on” and “off”, or “open” and “closed”,respectively, during and after (also respectively) dialysis sessions asfollows.

When both valves 150,160 are in the open condition, blood may flowbetween fistula 110 and both vein 2 and artery 4 and into properlyplaced needles 70,80 for performing hemodialysis. This is shown in theconfiguration of FIG. 3A. However, when both valves are adjusted to theclosed condition, as shown in FIG. 3B, blood is prevented from flowingfrom either vein 2 or artery 4 and into a substantial portion of fistula110. Accordingly, thrombosis, “steel” hand, and cardiac output concernsthat are often associated with the chronic shunting through long-term,indwelling AV-fistula's are mediated by the ability to prevent the shuntflow between hemodialysis procedures.

However, it is generally desired to remove blood from the region offistula 110 located between valves 150,160 in the closed condition overany substantial period of time, as a static reservoir is formed therethat could result in significant clot formation. Accordingly, the regionmay be purged of blood and replaced by other agent from needles 70,80.One mode forces blood out of fistula through open valves 150,160, asshown in FIG. 3C. Another mode closes one valve, such as valve 150adjacent vein 2, and then purges the fistula blood into artery 4 priorto closing valve 160 in a subsequent step; or, the opposite order ofvalve closing may be pursued, such as shown in FIG. 4D including phantomview of valve 160 (further described below). In addition, with bothvalves 150,160 closed, by providing a vacuum suction to lumen 133,allows lumen 133 to be evacuated, and according to suitable level ofvacuum and structure for wall 131 allows member 130 to collapse in anevacuated condition between treatments. Or, both valves can be closedand then an anticoagulant can be placed in the stagnant blood or canelute from the valve 170.

A common actuator assembly 95 may be coupled to each valve, inparticular when they are configured to turn “on” or “off” together atthe same time; or, such common actuator assembly 95 may be adapted toindividually actuate at separate instances or intervals. Moreover,independent actuators may be employed.

System 100 may be further modified to have only one valve 150 within thefistula 110, as illustrated by way of example by the embodiments shownin FIGS. 4A-D.

More specifically, system 101 in FIGS. 4A-B provides an embodimentwherein valve assembly 150 is located substantially in a central regionof fistula 110 between vein 2 and artery 4, which central valve 150 isshown open in FIG. 4A and closed in FIG. 4B. In this configuration, theability to purge the fistula 120 from blood during “off” periods isgenerally lost. However, the benefit of flow cessation of the shuntthrough the fistula 120 is retained, and the blood resident on eitherthe venous or arterial side of the valve 150 only occupies an area ofabout one-half the length of fistula 120, each end 122,124 being adaptedto mix with the adjacent flowing vessel.

A valve 150 having a position along only one anastomosis site, such asthe venous side 132, is shown in FIGS. 4C-D. After dialysis is finished,the valve 150 on the venous side 132 of fistula 130 is closed and thefistula 130 is flushed using one or both of needles 70,80 with asolution such as a fluid agent, which may contain for example anantithrombotic solution and/or a pharmaceutical inhibitor of neointimalhyperplasia, or other diagnostic or therapeutic agents as elsewhereherein described. In the interim between dialysis sessions, flowproceeds in the normal physiologic direction and the graft isessentially a column of stagnant anticoagulated fluid waiting to be usedagain. As mentioned above and shown in shadow in FIG. 4D, if there is asecond valve 160 at the arterial anastomosis side 134, then this valveis turned off after the flush as well, isolating the fistula contentsfrom blood until the next procedure.

Fistula valves according to the embodiments in FIGS. 3A-4D can be placedat the time of fistula creation (both artificial and native vesselfistulas), or placed into an artificial vessel prior to implantation.Seating regions built into a graft wall that makes up a fistula may bebuilt for example to interface with and permanently receive and house adetachable valve that might be delivered into the fistula translumenallyor otherwise. Or such valves themselves may include a mechanism to allowfor in-situ positioning and implantation within the fistula graft, suchas by piercing hooks or other fasteners for example that might extendaround a circumferential annulus surrounding the valve, and which may beadjustable from a retracted position for delivery to the location withinthe fistula, to an extended position for engaging the fistula graft wallto form the final integrated implant assembly.

Various different appropriate mechanisms may be used for valves 150 or160, as would be apparent to one of ordinary skill. In one embodiment,one or both of valves 150,160 are electromechanically activated. Whenthe dialysis access technologist is to initiate dialysis, the valves areactuated. According to another embodiment the valve is adapted to beferromagnetically actuated, such as by including a ferromagneticmaterial in the presence of an adjustable magnetic field actuator. Theapparatus is moved passively at the time of dialysis with an externalelectromagnetic actuator. The valve then is turned from the off positionto the on position via magnetic actuation and dialysis commences.

A further example of this embodiment is illustrated in FIGS. 5A-C anduses hydraulic actuation for valves 150,160. More specifically, valvesystem 170 includes a valve assembly 173 opposite valve assembly 177 ofsimilar construction and arranged in a similar manner to valve system 50shown in FIGS. 1B-1D. However, valve system 170 includes a wall 174 thatisolates valve system 170 between a first portion 175 and a secondportion 176. First portion 175 is fluidly coupled to valve 150 viaelongate tubular member 152; second portion 176 is fluidly coupled tovalve 160 via elongate tubular member 162. Each of valves 150,160includes an expandable member 154,164, respectively, that is adjustablebetween a radially collapsed condition and a radially expanded conditionrelative to the longitudinal axis L of the respective elongate tubularmember. As shown for illustration with respect to valve 150 in contextto a reference AV-fistula graft in shadow in FIGS. 5A-B, expandablemember 154 has a diameter d adapted to allow blood flow to passthereover, such as during hemodialysis procedure using needles throughvalve system 170 in a similar way previously described for valve system50. In the radially expanded condition shown in FIG. 5C, however,expandable member 154 has an expanded outer diameter D that is greaterthan collapsed diameter d and is adapted to substantially occlude flowthrough the reference fistula. This diameter D may be equal to, slightlyless than, or slightly greater than the general inner diameter of thegraft fistula in order to achieve the desired substantially occludedresult.

Expandable members 154,164 in one highly beneficial embodiment areinflatable balloons, and may be highly compliant or elastomeric, such aslatex, polyurethane, or silicone, or may have relatively less complianceor elasticity and assume a memory fold geometry (not shown) in thecollapsed condition. In the compliant variation, the material formingthe balloon skin preferably has an elastic elongation of at least 500%before reaching the outer diameter D, and may be up to about 700 toabout 900% elastic elongation, in any event optimized to preserve lowprofile within the graft lumen during the collapsed condition foroptimal blood flow. The balloons are inflated with pressurized fluidfrom a needle into the chamber(s) of valve system 170, and remaininflated upon removal of the needle as there is an external seal atvalve assembly 153, in a similar manner to that described for fluidagent delivery via valve system 50 in FIGS. 1B-D.

A grating valve structure similar to grating 60 in FIGS. 2A-D may beutilized for the present embodiment of FIGS. 5A-C, wherein the gratingis designed to allow for sufficient fluid pressure retention within thechamber of valve portions 175,176 to allow for inflation of balloons at154,164 via pressure injection from needles into portions 175,176.Moreover, these independent valve portions 175,176 allow for independentcontrol over valves 150,160. This is shown for example in FIG. 5B withneedle 70 injecting fluid into portion 175 of valve system 170. Though,alternative embodiments contemplate a more unitary chamber constructionwith one common fluid actuation.

In either the embodiments shown schematically in FIG. 3A-C, 4A-B, or4C-D, a significant benefit is provided to the patient by not having ablood-shunting fistula when not on dialysis. The conventional fistulaper se has its own morbidity. It increases circulating volume andcardiac output by 20%, thus straining the heart. Furthermore, manypatients complain of a steal syndrome to their hands in which too muchblood is shunted away from their hands, leading to ischemia. Moreover,neointimal hyperplasia may also be thwarted at the anastomotic sitesbecause there is no flow most of the time. The risks and extent of thesepotential problems are reduced by these embodiments of the presentinvention.

Drug Eluding AV-Fistula Graft

A further embodiment of the invention is provided in FIGS. 6A-7B,wherein certain aspects of an AV-fistula are specially adapted toprevent neointimal hyperplasia associated with chronic implantation, andin particular with respect to the respective venous and arterialanastomosis sites, and still more particularly with respect to venousanastomosis site.

More specifically with respect to the embodiment shown in FIG. 6A, anAV-fistula 200 includes an elongated body 201 with an outer graft member210 that is shown coaxially disposed around an inner liner 220. Outergraft member 210 defines an inner lumen 205, and may be constructed ofsimilar design and materials as standard AV-fistula graft materials.

Inner liner 220 extends beyond at least one end of outer graft member210 and terminates at an end 222 that corresponds to end 202 ofAV-fistula. Inner liner 220 may also extend within outer member 210 allthe way to the other end 204 of body 201 that corresponds to the end 214of outer member 210. Or, inner liner 220 may terminate beyond the otherend 214 of outer member 210 and constitute the other end 204 of body201. Still further, inner liner 220 may terminate within outer member210, such as is shown at end 225, which may be for example a point ofattachment between liner 220 and outer member 220, leaving the rest ofinner liner 220 “free floating” within outer member 220.

In any event, inner liner 220 where it extends from the end 212 of outermember 210 is adapted to form a seal over the anastomosis area betweenouter graft member 210 and the corresponding vein or artery. This sealis adapted to prevent significant exposure to blood factors within thevessel to the anastomosis area, which is predicted to result inprevention of neointimal hyperplasia that has otherwise been observed tooccur at such anastomoses. In the event inner liner 220 extends beyondonly one of the ends 212,214 of outer graft member 210 for such purpose,this would typically be located along the venous anastomosis end whenplaced in-vivo, since this is the site for most frequent occurrence ofthe hyperplasia condition.

Inner liner 220 is generally more flexible, and typically much moreflexible, than the outer graft member 210, such that pressure from bloodflow acts to effectively “stent” the liner 220 against the wall to formthe desired seal across the anastomosis. In one particular mode, theliner 220 is a membrane of flexible material, and is substantially thinand shaped to provide the intended result just described at the desiredanastomosis site. The anastomosis is sewn over the membrane. Afterward,the blood flow through the fistula and its associated pressureeffectively stent the membrane open against the vein wall.

In addition, inner liner 220 in the embodiment shown in FIG. 6A is also“doped” with a bioactive agent, such as pharmaceutical inhibitor ofneointimal hyperplasia or anti-thrombotic, or other agents hereindescribed or apparent to one of ordinary skill.

Such agent may be provided as an interior coating 230, per the variationshown, that may extend along the liner length, or be localized toprimarily the region of the intended anastomosis site and where liner220 extends. Such coating may be a direct layer of the agent, which maybe in for example solid, gel, or paste form deposited along a surface ofthe liner 220. Or the coating may include at least one additionalcoating material to assist in adhesion and desired elution rate of thebiologically active agent. A layered structure of members may alsoprovide for a reservoir-type housing to hold the agent that eludesthrough one of the layers into the desired area. Such agent may also beimpregnated, adsorbed, or otherwise incorporated into the membrane.Physical pores or other structures may also be provided along liner 220to house the agent that then leaches therefrom. In one highly beneficialmode, the device 200 is constructed such that the pharmaceuticalinhibitor or other agent is released in a controlled manner over time.

Coating 230 is shown in FIG. 6A along an inner surface 223 of liner 220for the purpose of illustrating one mode. However, because neointimalhyperplasia takes place within the vessel wall, the opposite outersurface 224 may also be the location for providing the coating, as shownat coating layer 234.

Thus, according to the foregoing embodiments, neointimal hyperplasia maybe prevented in an AV-fistula, and in particular at its anastomosis, andfurther in particular at the venous anastomosis, by both shielding theanastomosis from turbulent flow, and by slow release of thepharmaceutical.

A further embodiment shown variously in FIGS. 6B-6G provides anastomosisextension or liner 220 with a plurality of longitudinal,circumferentially positioned members or fingers 227 that may be formedfor example by cutting slits in an annular tubular member as shown at220 in FIG. 6A. These slits may extend within the internal lumen ofouter body 210, as shown in FIG. 6C, or may be unitary within body 210for example for better adhesion. Fingers 227 are useful in aiding theability to position extension member 220 into the lumen of vein 2 duringa suturing procedure for anastomosing. As shown in FIG. 6C, a rearsuture 240 is completed before a top suture 242. During the suturingprocess, sutures may be formed between fingers 227, or at the locationof slits separating them. The fingers may be placed within the lumen ofthe vein 2 between each suture, aiding in the ease and accuracy of theprocess. A final anastomosed end-to-end anastomosis is shown in FIG. 6Cfor further illustration.

The design of FIG. 6B also allows for side anastomosing, as shown inFIGS. 6F-G. More specifically, the fingers 227 on the “upstream” side ofthe AV-graft 201 may be removed, such as by cutting them, allowing thedownstream side fingers 227 to be positioned to their ends 222 againstthe inner wall of vein 2 under the pressure of downstream blood flow, asshown in phantom and by aid of a reference arrow showing the deflectionunder blood flow. In addition to cutting certain of the fingers 227themselves, their length may also be custom trimmed by the healthcareprovider prior to a surgical anastomosis, such that the initial assemblymay be provided particularly long to provide for custom trimming to meetmost anticipated needs. Further to the embodiment providing onlydownstream fingers 227, it is also contemplated that an alternativegraft to that shown in FIG. 6B may be provided within fingers 227 onlyon one circumferential aspect of the graft for use in this type of sideanastomosing.

In another embodiment of the invention shown in FIG. 7A, an AV-fistulagraft 280 includes an elongate body 281 having a graft wall 282 thatdefines a lumen 285 that extends between ends 283,284. A pharmaceuticalpreparation or other biologically active agent is impregnated into theentire graft wall 282 so that the graft itself becomes thepharmaceutical reservoir. The agent is slowly released into the laminarboundary layer of the blood flow through the graft lumen 285, as shownin FIG. 7A by way of small flow arrows. Being approximately stagnant atthe edge of the boundary layer, the elution profile for the agent fromthe graft into that layer may be largely dependent on diffusion.

As also shown, the biologically active agent may also be adapted toelude more aggressively along at least one end 283,284, where stenosesare most frequently found. This may be done by providing more agentthere, such as in higher concentration preparations. Or, the onlylocation that the agent is deposited may be along such ends. Only oneend may also provide for the drug elution, which would more often be thevenous anastomosis end in use.

A further embodiment is illustrated in FIG. 7B, wherein a separatereservoir is coupled to the graft fistula 280 and is adapted to deliverbiologically active agent over prolonged periods of time into thedesired regions of the graft. Such reservoir may be located closelyadjacent graft fistula 280, such as on or adjacent to an outer surfacethereof, or may be more remotely located such as in another area of thebody or even externally of the body. The reservoir may also be locatedand designed in a manner that allows it to be refilled, such as throughneedle penetration of a sealing membrane or valve, as elsewheredescribed. In addition, the coupling to the graft may include severalpaths, such as for example two paths at each of two end portions 286,288of the graft fistula 280 where anastomoses are to be formed.

FIG. 7C shows further detail of one further beneficial variation for theembodiment shown in FIG. 7B, and includes an annular fluid bladder 290associated with an AV-graft body 281. In particular, FIG. 7C showsbladder 290 imbedded within graft body 281, and includes a porous innerwall 293 with a plurality of pores 295 located to infuse drug or otheragent internally through the inner aspect of wall 281 and into therespective AV-fistula lumen. A further more detailed view of such abladder having a tubular shape with a length L is shown in FIG. 7D.Length L is to be adapted for the particular application, but in generalis considered to be optimized to provide the local agent deliverynecessary to achieve the intended therapeutic or prophylactic result atan anastomosis region. Bladder 290 includes a coupling stem 297 thatextends from body 281 and is fluidly coupled to remotely located source289, which again may be refillable, and may be within the body orexternally located.

Bladder 290 may be formed from many different suitable materials andaccording to many suitable methods as would be apparent to one ofordinary skill. In one variation, bladder 290 is constructed from ametal ring or tube, such as sealed coaxial metal hypotubes, which metalmay be for example stainless steel or a nickel-titanium alloy. Inanother beneficial variation, the bladder 290 is of polymericconstruction, such as polyethylene, silicone, polyurethane, hytrel,nylon, or PEBAX™. Suitable exemplary methods for forming such polymerictube or ring include without limitation a free-blowing or blow moldingprocess, or other form of molding such as injection molding.

The pores 295 may be discretely formed annular regions in the bladderwall, such as by laser drilling, mechanically drilling, electronicdischarge, or other suitable post-processing techniques. The dimensionsof the pores may be variable, and may depend for example on themolecular weight or viscosity of the agent to be delivered, deliveryprofile desired. Or, they may be variable within a particular bladderitself to achieve variable delivery over different areas, e.g. moreaggressive delivery closest to the ends. Nevertheless, for the purposeof illustration, suitable embodiments provide the pores with diametersbetween about 0.1 mm to about 1 mm, and may be about 0.5 mm for certainapplications. Alternatively, the membrane forming bladder 290 may be a“micro” porous material, such as certain suitable known forms of PTFE.One such suitable material process for example provides PTFE with anetwork of interconnected microfibrils with gaps therebetween. The gapsare filled with a material that may be controllably removed by exposureto a solvent. According to the present embodiment of the invention, byproviding the solvent process only along the surface intended to be theinternal surface of the bladder 290, the internally pored structure maybe achieved without providing leaking pores along other circumferentialregions of the bladder 290 (thus isolating the agent delivery only tothe internal lumen). Or, it should be further appreciated that thelocalized interior porosity is a beneficial variation but not alwaysnecessary, and porosity may be provided elsewhere including alllocations along bladder 290 with respect to graft member 281.

Bladder 290 may be positioned internally within or externally aroundgraft wall 281, depending upon the particular application, and need notbe embedded therein. In this regard, bladder 290 may be provided incombination with graft body 281 by a manufacturer, such as in apre-packaged sterilized assembly. Alternatively, bladder 290 may beprovided separately for final assembly by an end user prior to asurgical anastomosis. However, the embedded variation is consideredhighly beneficial for chronic implantation in a blood field.

Energy Treatment of AV-Fistulas

The present invention also provides for highly beneficial system andmethod for coupling energy to regions of implanted AV-fistula grafts,such as at their anastomoses, in order to prevent or otherwise treatformation of occlusive stenoses. In particular, such systems and methodsare adapted to provide such energy coupling by use of passive treatmentassemblies positioned along the AV-fistula graft that are actuated byexposure to an externally applied energy field. This allows for routinemaintenance treatments with significantly reduced costs and complexityto other previously disclosed invasive systems that require activeenergy delivery sources to be introduced into a fistula during each timefor energy treatment. Therefore, maintenance may be done more frequentlyfor more efficacious prevention. In addition, the present systems andmethods provide for prevention of both neo-intimal hyperplasia, as wellthrombus formation or adhesion to grafts or their anastomosed vessels.The treatment assembly may be provided on a disposable deliveryplatform, whereas the remote energy source for applying the actuatingfield may be an implant or otherwise reusable, in particular forembodiments that allow for transcutaneous application of the actuatingenergy field. The treatment assembly not requiring an active energysource is also adapted to be made sufficiently small and flexible to bedelivered into a lumen of a graft for treatment through a hemodialysisneedle. Further aspects of these benefits will be further appreciated byreference to more detailed descriptions of the particular exemplaryembodiments as follows.

One particular beneficial embodiment related to this aspect of theinvention is shown in FIG. 8A as follows. A hemodialysis system 400 isprovided with an AV-fistula 410 that is constructed and operated in amanner such that energy may be coupled between the fistula 410 and anarea adjacent thereto. This coupled energy is adapted to prevent orremove stenosis, such as thrombus or neointimal hyperplasia.

An energy source 450 is provided that transduces a first energy field toa treatment region 417 of the graft 410, which transduction is generallyacross a skin layer 5 wherein the energy source 450 is locatedexternally of the body (though may be done more invasively, such as byan implanted energy source). This energy is then coupled by the fistula410 to the surrounding area, typically at a location intended to disturbthe growth of neointimal hyperplasia on a regular basis so as not toallow it to form, or to inhibit thrombus formation or adhesion. Or theenergy coupling may be performed more acutely in order to remove eitheror both components of stenosis.

The treatment region 417 is generally incorporated into graft 410 and isadapted to be implanted therewith at the time of surgery, and the can beplaced anywhere along the graft 410 but preferably at an intendedanastomosis region, most preferably at least at the intended venousanastomosis region, where problems occur after implantation of thegraft.

In one embodiment, the treatment region 417 includes a material, such asa coating, which absorbs a specific wavelength of light. For example, aUV-absorbing material may be used in conjunction with an energy source450 that is a UV light source. Or, infrared light absorbance may beprovided in an additional or alternative mode. The material coating canbe attached to a flexible material which then extends from the graft,covering the inside portion of the graft fistula 410, such as is shownat inner liner 420 secured to inner surface 413 of graft body 410 andextending from end 412 of outer graft body 410 to terminal end 422.Inner liner 420 is thus similar in arrangement to inner liner 220 inFIG. 6A with respect to the corresponding graft body. This arrangementtherefore places the treatment region 417 along a covering to ananastomosis, as well as combines the benefits of such a covering asdescribed above. As described before for such a liner, the treatmentregion 417 may extend elsewhere along the graft, such as to end 424corresponding to end 414 of graft 410, or terminate within an interiorregion such as at end 425.

However, the present embodiment benefits from energy coupling ratherthan localized fluid agent delivery under the previous embodiment.Further acceptable variations that may assist in such energy couplinginclude metallic material such as stainless steel or nickel-titaniumfoils, or fine wires or wire meshes. Further variations includecombination of nickel titanium and/or stainless steel and a flexiblematerial polymer such as silicone or PTFE, and can comprise PTFE orsilicone or other polymeric membrane doped with ferromagnetic particlesor drug releasing particles.

The material chosen for liner extension 420 according to one beneficialvariation is flexible and may have several longitudinal slits formedtherein in a similar manner to that previously disclosed above byreference to FIGS. 6B-G, such that when blood flows through it, thematerial is stented against the vessel wall. Various more detail of thearrangement of such fingers according to the present embodiment is shownin FIG. 8B, and in FIG. 8C in the context of a side anastomosis, and inFIG. 8D in the context of an end-to-end anastomosis. FIG. 8D also showsenergy source 450 schematically coupled across skin layer 5 to treatmentregion 417 for the purpose of further illustration, and similar couplingis contemplated for the side anastomosis in FIG. 8C though not shown forsimplicity.

The specific embodiment shown in FIG. 8 provides the treatment region417 along an inner liner extension 420 similar to that described abovewith respect to FIGS. 6A-B,

In another embodiment, the treatment region 417 extending from the end412 of the graft 410, again preferably near the intended venousanastomosis, contains a ferromagnetic material which is responsive to anelectromagnetic energy source 450 from above the surface of the skin ofthe patient. After or during dialysis, the technician applies the energysource to the region of the anastomosis, causing a rapid mechanicalvibration of the material. The vibration prevents or disturbs theoccurrence of neointimal hyperplasia at the site.

In general, when the treatment region 417 is warmed at the region of theanastomosis, neointimal hyperplasia is inhibited or disturbed. Thisprocedure would generally be done at the time of dialysis after orduring a run three times a week and is meant to prevent neointimalhyperplasia.

It is to be appreciated that in the embodiments just described or othervariations therefrom that may become obvious to one of ordinary skill,the treatment region 417 may provide the prophylactic or remedial energycoupling into the surrounding area by heating that area, such as fromwarming due to the energy coupling to the treatment region 417 from theenergy source. However, other energy coupling modes are contemplated aswell according to other mechanisms known in the art, such as for exampleby use of fluorescence provided by the material along the treatmentregion 417, or otherwise.

A further highly beneficial embodiment is variously illustrated in FIGS.9A-D. According to this embodiment, a system 500 is provided that alsoallows for energy coupling between a treatment device and an areaassociated with an implanted AV-fistula 510. However, according to thishighly beneficial embodiment, a separate catheter device 550 is used toachieve the energy coupling during periodic, less-invasive introductioninto the fistula lumen 515.

Catheter device 550 is shown schematically in FIG. 9A, and includes anelongate body 551 that extends between a proximal end 552 and a distalend 554. A treatment assembly 555 is located along distal end portion554. Treatment device 555 is adapted for use in coupling the highlybeneficial therapeutic or prophylactic energy within an AV-fistula 510according to the invention as follows.

Referring to FIG. 9B, a typical dialysis system 500 and procedure isdepicted, in the sense that an AV-fistula 510 is shown extending betweenanastomosis sites at its ends 512,514 with a vein 2 and an artery 4, andfurther with respect to hemodialysis needles 70,80 being located withinthe fistula 510. However, FIG. 9B further illustrates an initial mode ofusing catheter device 550 of this embodiment as follows.

Distal end portion 554 of catheter 550 is constructed of appropriatedimension, design, and material such that it is adapted to be advancedthrough a dialysis needle 80 and into lumen 513 of fistula 510 such thattreatment assembly 555 is located adjacent to the area to be treatedwith applied energy. Therefore, distal end portion 554 is dimensioned tofit within typical dialysis needles, that are generally between about 16and about 18 Gauge, or having an inner diameter between about 1.5 andabout 1.0 millimeters. Accordingly, distal end portion will typicallyhave an inner diameter that is no larger than those needle innerdiameters, and more preferably provide at least 0.005″ clearance withinthose bores. In addition, the treatment assembly 555 is constructed ofappropriate design and material to have appropriate flexibility (orconversely stiffness) to be appropriately positioned in the mannerdescribed within the graft 510. Polymeric materials such aspolyethylene, nylon, PEBAX™, polyurethane, copolymers, or the like, orcombinations thereof or composite constructions therewith, may besuitable materials for forming body 551 at least along distal endportion 554. In addition, body 551 proximally of treatment assembly 555,may be made relatively less flexible with greater stiffness, allowingfor advancement through a tight tolerance within a needle.

Still further, distal end portion 554 may be made trackable within graftlumen 513. This may be accomplished by providing a guidewire lumen (notshown) through body 551 that is adapted to slidably engage and trackover a guidewire that may be first positioned along the area fortreatment. In another variation, distal end portion 554 may also bearticulated, such as by providing a pull wire secured to the distal end554 and that is retractable through a lumen in body 551 by proximalmanipulation outside the body, such as via a coupler shown schematicallyat coupler 553. Other articulation or tracking mechanisms may besuitable as would be apparent to one of ordinary skill.

In any event, as shown in further detail in the exploded view in FIG.9C, treatment assembly 555 is positioned at a location where a stenosis6 has developed at an end 514 of fistula 510 that is anastomosed tovessel 4, such as at a vein stenosis. Treatment assembly 555 is thenactivated to couple an energy field 558 to the surrounding area thatincludes stenosis 6. By supplying the appropriate energy, stenosis 6 isreduced, which may be by any appropriate mechanism, such as for examplewithout limitation by: ablation, destruction, removal, destruction,desiccation, shrinkage, or expansion or dilation. Mechanical energy maybe an appropriate form of energy coupling in some circumstances.However, in highly beneficial aspect of the invention non-mechanicalenergy coupling is contemplated, such as for example thermal energy,light energy, electrical energy, magnetic energy, etc. Moreover,treatment assembly may emit energy, such as light, thermal, orelectrical current. Or, cryogenic coupling may be used, such as byactively cooling treatment assembly 555 in order to cool the surroundingstenotic area by removing thermal energy therefrom.

In a highly beneficial, preferred mode shown in FIG. 9D, a remote energysource 580 is used to first couple energy to treatment assembly 550,which may be in the mode shown across a skin layer 5 of the patient, andmay be in a still further preferred mode thermal, light, or inductiveenergy coupling through the intervening tissues and without requiring“hard-wired” coupling to the treatment assembly 555. This allows forsignificant simplicity of use, wherein the energy source 580 is placedagainst or next to the skin closest to the treatment assembly 555 belowand is activated to couple the energy needed. After receiving theenergy, the treatment assembly then is activated to undergo energycoupling to the surrounding area, such as provided above by warming orfluorescing or reflecting light or otherwise. This energy couplingarrangement is further illustrated by way of bolded arrows in FIG. 9D.

The treatment assembly may also include a radially expandable memberthat is adjustable between a radially collapsed condition with a firstouter diameter d and a radially expanded condition having a second outerdiameter D greater than the first outer diameter. Such an expandablemember 556 is shown schematically in cross-section in the radiallyexpanded condition in FIG. 9D, and further in phantom in the radiallycollapsed condition designated at 556′. By providing for this radialadjustability, the assembly 555 is adapted to be delivered through adialysis needle in the radially collapsed condition, and then expandedwithin the anastomosis to the radially expanded condition. The treatmentassembly 555 is adapted to couple the energy to the area surrounding theexpandable member 556 in the radially expanded condition. Therefore, agreater area may be treated by the energy coupling around the expandedmember 556.

Various types of radially expandable members have been previouslydisclosed and are suitable for use for member 556 as just described. Inone beneficial mode, the member in the expanded condition is adapted toprovide a substantially circumferential pattern of energy, such as anexpandable annular or tubular member. Of further benefit, the expandablemember is an inflatable balloon, and may be coupled for example to apressurizeable source of fluid, such as via coupler 553 and source 560shown in FIG. 9A. Such balloon may include a material associated withits balloon wall that couples the required energy as described, or theinflation medium itself may be adapted to provide for such coupling. Inone particular such example, the inflation medium is adapted to eitherheat when exposed to a sonic energy field, or otherwise absorb ortransmit such energy in a manner that provides the desired coupling. Theenergy source 58 thus sonifies the medium that is activated asdescribed. Moreover, internal energy sources may be used within such aballoon, such as ultrasound crystals disposed therein.

The device 550 just described may be adapted for resterilization andreuse after providing the desired treatment, or may be adapted forsingle-use only. Moreover, while the catheter 510 is herein described byreference to delivery through a dialysis needle, other modes arecontemplated, including without limitation delivery through either ofthe vein or artery anastomosed to the fistula, or transcutaneously anddirectly into or adjacent to the graft fistula, as would be apparent toone of ordinary skill.

In addition to providing the ability to remedially treat and reduceAV-fistula stenosis, the embodiments just described enjoy the benefit ofproviding a prophylactic solution to AV-fistula stenosis that may beperformed on a maintenance basis. Rather than allowing the accessfistula to malfunction before treatment, the system 500 is used at thetime of dialysis, e.g. once per week, and using pre-existing needleaccess site. This disturbs development of hyperplasia along the accessfistula, thwarting its development before it begins. In addition, thelogistics provided by this system 500 are optimized. For example, apatient does not have to be transported to a specialized angiography orinterventional radiology suite for care of the dialysis access. Theprocedure can be performed if desired just after the patient isundergoing dialysis, and avoids additional punctures of the accessfistula that eventually lead to aneurysms or other adverse acute andlong-term effects.

According to the various embodiments described above, standardAV-fistula graft materials and designs may be used except whereotherwise indicated according to the particular aspects associated witheach embodiment. Examples include materials such aspolytetrafluoroethylene (PTFE), Dacron™, or other commonly usedmaterials. More specific examples may include grafts of the typecommercially available from companies such as GORE™ or IMPRA™Corporations.

Various modifications may be made to the embodiments by one of ordinaryskill without departing from the intended scope of the presentinvention. For example, the various system, device and correspondingmethod embodiments may be applied to autogenous or artificial AV-fistulagrafts, though one particular type may be shown and described for thepurpose of illustrating a particular embodiment. In another example, thevarious embodiments may be adapted for use in other fistulas or medicallumen junctions other than the AV-fistula grafts herein shown anddescribed without departing from the invention (though clearly theinvention provides significant particular benefit for AV-fistula graftapplications in hemodialysis). Further more specific examples of suchfurther junctions for use in combination with the present embodimentsinclude without limitation: anastomotic junction between a brachialartery and a basilic vein; and anastomotic junctions at either ends ofcardiac bypass grafts. In addition, despite the particular benefitsprovided for the specific embodiments herein shown and described, theymay be combined, or aspects thereof, where appropriate to meet aparticular need. For example, various of the graft embodiments shown ordescribed without certain specific valves provided by other embodimentsmay nevertheless include the valves according to such other embodiments,as may be appropriate for a particular case. In another specificexample, fistula valves shown and described by reference to FIGS. 3A-4Dmay be further modified to provide for energy delivery to surroundingareas as treatment assemblies for similar use in treating anastomoticstenoses as described for treatment assemblies of FIGS. 8A-D. In anothermore specific example, balloons provided for valve purposes according toFIGS. 5A-C may also provide balloon-based treatment assemblies, ineffect combining aspects of the embodiments of FIGS. 8A-D and FIGS.9A-D. Moreover, where treatment methods or device features are shown ordescribed by reference to a specific location relative to a fistulagraft (e.g. at a particular anastomosis site), other locations arecontemplated.

In another regard, the invention contemplates each individual deviceherein described as a beneficial embodiment when taken alone, and shouldnot be considered limited to use or combination with others of theembodiments. Notwithstanding the foregoing, combinations andsub-combinations of the assemblies and methods of the variousembodiments are also contemplated as highly beneficial; and thus thevarious systems and overall procedure methods formed thereby are alsocontemplated as individually beneficial aspects of the invention. Inthis regard, other devices such as needles, pumps, syringes, etc. mayalso be combined to form total systems that may be advantageouslypackaged or sold together as an overall system for performing dialysis.

The embodiments have also been herein described in relation to theirhighly beneficial use and adaptation for hemodialysis procedures.However, it is further contemplated that the various devices and methodsmay be applied to other procedures or systems for use in treating ordiagnosing other indications or conditions without departing from theintended scope.

Although the description above contains many specificities, these shouldnot be construed as limiting the scope of the invention but as merelyproviding illustrations of some of the presently preferred embodimentsof this invention. Therefore, it will be appreciated that the scope ofthe present invention fully encompasses other embodiments which maybecome obvious to those skilled in the art, and that the scope of thepresent invention is accordingly to be limited by nothing other than theappended claims, in which reference to an element in the singular is notintended to mean “one and only one” unless explicitly so stated, butrather “one or more.” All structural, chemical, and functionalequivalents to the elements of the above-described preferred embodimentthat are known to those of ordinary skill in the art are expresslyincorporated herein by reference and are intended to be encompassed bythe present claims. Moreover, it is not necessary for a device or methodto address each and every problem sought to be solved by the presentinvention, for it to be encompassed by the present claims. Furthermore,no element, component, or method step in the present disclosure isintended to be dedicated to the public regardless of whether theelement, component, or method step is explicitly recited in the claims.No claim element herein is to be construed under the provisions of 35U.S.C. 112, sixth paragraph, unless the element is expressly recitedusing the phrase “means for.”

1. An AV-fistula graft, comprising: a tubular graft body having a firstend portion, a second end portion, and a graft lumen extending betweenfirst and second ports located at the first and second end portions,respectively; and means for coupling energy to an area corresponding tothe tubular graft body sufficient to cause a therapeutic effect in apatient when the AV-fistula graft is implanted within the patient andextending between two opposite anastomoses associated with a vein and anartery, respectively.
 2. The AV-fistula graft of claim 1, wherein themeans for coupling energy to the area further comprises means forresponding to an applied energy field from a remotely located energysource.
 3. The AV-fistula graft of claim 2, wherein the means forcoupling energy to the area further comprises means for applying theenergy field to the responding means from a remotely located energysource.
 4. The AV-fistula graft of claim 3, wherein the applying meanscomprises means for applying the energy field to the responding meansacross a skin barrier of the patient.
 5. The AV-fistula graft of claim2, wherein the coupling means further comprises a material that exhibitsa material response to the applied energy field.
 6. The AV-fistula graftof claim 1, further comprising means for positioning the energy couplingmeans at a location along the AV-fistula graft during energy coupling tothe area from the energy coupling means.
 7. An AV-fistula graft systemto maintain patency, comprising: a tubular graft body having a first endportion, a second end portion, and a graft lumen extending between thefirst and second end portions, respectively; and an energy couplingsystem comprising light which is configured to deliver a dose of lightenergy sufficient to inhibit intimal hyperplasia at or near the first orsecond end portions.
 8. An AV-fistula graft system to maintain patency,comprising: a tubular graft body having a first end portion, a secondend portion, and a graft lumen extending between the first and secondend portions, respectively; and an energy coupling system comprisingultrasound which is capable of delivering a dose of vibrational energysufficient to inhibit intimal hyperplasia or break up a clot at or nearthe first or second end portions.
 9. An AV fistula graft system tomaintain patency, comprising: a tubular graft body having a first endportion, a second end portion, and a graft lumen extending between thefirst and second end portion, respectively; a treatment apparatusconfigured to couple energy from an external source, through the skin,and to the treatment assembly wherein the coupled energy inhibitsneointimal hyperplasia or breaks up a clot.